BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans ; Ubiquitin-Protein Ligases/physiology* ; Bone and Bones/metabolism* ; Animals ; Tripartite Motif Proteins/physiology* ; Osteoclasts/metabolism* ; Osteoblasts/metabolism* ; Signal Transduction/physiology* ; Osteogenesis/physiology*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Abstract Postoperative urinary retention is a common complication after mixed hemorrhoid surgery, referring to the inability of urine in the bladder to be normally expelled, leading to urine retention. This condition not only prolongs the postoperative recovery time and increases medical costs, but may also cause problems such as urinary tract infections and bladder dysfunction. The pathogenesis of urinary retention after mixed hemorrhoid surgery is complex, involving multiple factors such as the type of surgery, anesthesia method, individual differences among patients, postoperative pain management and psychological stress. Although there are various clinical treatment methods, their efficacy varies among individuals. This article reviews relevant literature from 2018 to 2024, analyzing the etiology of urinary retention after mixed hemorrhoid surgery. It summarizes the intervention measures and mechanisms of non-pharmacological treatments, such as physical therapy and analgesic techniques, as well as pharmacological treatments, including anticholinesterase drugs, selective α-receptor blockers and analgesics drugs, so as to provide the reference for the prevention and treatment of urinary retention after mixed hemorrhoid surgery.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

ObjectiveTo identify the main chemical constituents of Anmeidan （AMD） and to explore the mechanism of AMD in regulating the extracellular signal-regulated kinase 1/2 （ERK1/2）/mitogen-activated protein kinase （MAPK）-interacting serine/threonine-protein kinase （MNK）/eukaryotic translation initiation factor 4E （eIF4E） signaling pathway to improve circadian rhythm disturbances in insomnia rats. MethodsThe main chemical constituents of AMD were identified using ultra-high-performance liquid chromatography-linear ion trap-electrostatic orbital trap mass spectrometry （UPLC-LTQ/Orbitrap/MS） in combination with reference standards. Sixty male Sprague-Dawley （SD） rats were randomly divided into control， model， melatonin， and AMD low-， medium-， and high-dose groups， with 10 rats in each group. Except for the control group， all rats were administered p-chlorophenylalanine via intraperitoneal injection to establish an insomnia model. The activity-rest rhythm of rats was assessed using the open field test and circadian rhythm test. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe structural changes in hypothalamic neurons. Immunofluorescence， real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis were employed to detect mRNA and protein expression levels of ERK1/2， MNK， and eIF4E in the hypothalamus. ResultsA total of 50 chemical components， including flavonoids， phenylpropanoids， triterpenoid saponins， alkaloids， and lignans， were identified in AMD. Compared with the control group， the model group exhibited significantly increased total distance traveled， average speed， central area residence time， and cumulative rearing time （P<0.01）， as well as prolonged cumulative activity time and total activity time in both light and dark phases （P<0.01）. Hypothalamic neurons in the model group were sparsely arranged， reduced in number， and exhibited nuclear disappearance or nucleolar rupture， with a significantly increased apoptosis index （P<0.01）. The cytoplasm appeared turbid， Nissl body staining was lighter， and the Nissl body apoptosis index was significantly increased （P<0.01）. The mRNA expression levels of ERK1/2， MNK， and eIF4E were significantly decreased （P<0.01）， along with a significant reduction in protein expression levels of ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， MNK， phosphorylated MNK （p-MNK）， eIF4E， and phosphorylated eIF4E （p-eIF4E） （P<0.01）. Compared with the model group， the total distance， average speed， central area residence time and body upright cumulative time of the AMD high-dose group were significantly reduced （P<0.01）. The total distance， average speed and body upright cumulative time of the AMD medium-dose group were significantly reduced （P<0.01）. The cumulative time of light activity and total time of activity in each dose group of AMD were significantly shortened （P<0.01）. The cumulative time of dark activity in the high-dose group of AMD was prolonged （P<0.01）. The neurons in the middle and high dose groups of AMD were closely arranged， the number of neurons increased， and the apoptosis index of hypothalamic cells decreased significantly （P<0.05， P<0.01）. The cytoplasm of the low， middle and high dose groups of AMD was clear， the color of Nissl body became darker， and the apoptosis index of Nissl body decreased significantly （P<0.01）. The expression of ERK1/2， MNK and eIF4E mRNA and protein in the hypothalamus of the middle and high dose groups of AMD increased significantly （P<0.05， P<0.01）. ConclusionAMD primarily contains 50 chemical constituents， including flavonoids， phenylpropanoids， and triterpenoid saponins. It exhibits a "synergistic enhancement" effect through multiple components and multiple pathways to improve insomnia. AMD ameliorates circadian rhythm disturbances in p-chlorophenylalanine-induced insomnia rats by upregulating ERK1/2/MNK/eIF4E signaling pathway-related proteins.

Objective:To observe the adaptive changes in the cardiovascular system after travelling to high altitude in healthy people using supine bicycle exercise stress echocardiography（SE），and to reveal the changes in right heart function，pulmonary vascular reserve and right ventricular systolic reserve in healthy people after acute high altitude exposure.Methods:Thirty-six healthy adults were prospectively collected to undergo SE at low altitude（500 m）and high altitude（3 600 m）. Offline analysis was conducted to acquire resting and peak exercise ultrasound parameters at high and low altitudes：tricuspid regurgitant velocity（TRV），tricuspid annular peak systolic velocity（TV-s′），right ventricular end-diastolic area（RVEDA），right ventricular end-systolic area（RVESA），right ventricular fractional area change（RVFAC），right ventricular basal transverse dimension（RVD1），right ventricular mid-ventricular transverse dimension（RVD2），right ventricular longitudinal dimension（RVD3），right ventricular free wall longitudinal strain（RVFWS），right ventricular global longitudinal strain（RVGLS），left ventricular cardiac output（CO），pulmonary artery systolic pressure（PASP），mean pulmonary artery pressure（mPAP），pulmonary resistance（PVR）and the ratio of tricuspid annular systolic displacement（TAPSE）to PASP（TAPSE/PASP）. The pulmonary vascular reserve and right ventricular systolic reserve indices including pulmonary vascular reserve and right ventricular systolic reserve indices（mPAP/CO slope，change in tricuspid annular systolic displacement（ΔTAPSE），change in fractional area change（ΔRVFAC），change in overall long-axis strain of the right ventricle（ΔRVGLS），and change in peak velocity of the lateral wall of the tricuspid annulus（ΔTV-s′）were calculated. The differences of these parameters betweet high and low altitudes were compared.Results:During the resting period，the values of TRV，PASP，mPAP，PVR，RVD2，and RVD3 were higher at high altitude than at low altitude（all P<0.05）. TAPSE/PASP，RVFAC，RVGLS，and RVFWS were lower at high altitude than at low altitude（all P<0.05）. During the peak exercise period，TRV，PASP，mPAP，PVR，RVAD，RVAS，RVD2，and RVD3 were all higher at high altitude than at low altitude（all P<0.05），and RVFAC at high altitude was lower than at low altitude（ P<0.05）. Right ventricular systolic reserve and pulmonary vascular reserve：mPAP/CO slope at high altitude was higher than at low altitude，ΔTV-s′ and RVFAC were lower than at low altitude（all P<0.05），there were no significant differences in ΔTAPSE and ΔRVGLS between the two altitudes（all P>0.05）. Conclusions:Acute high altitude exposure causes adaptive dilatation of the right ventricle accompanied by a reduction in pulmonary vascular reserve and right ventricular contractile reserve function.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Aim To explore the material basis and un-derlying mechanism of Qingre Huoxue Formula(QRHXF)in the treatment of non-small cell lung cancer(NSCLC)by applying network pharmacology,molecular docking technology and bioinformatics com-bined with animal experiments.Methods TCMSP,ECTM,and BATMAN databases were used to obtain active components and corresponding targets of QRHXF;GEO and DisGeNENT databases were con-ducted to acquire NSCLC-associated differential expres-sion genes.By intersecting them,the common targets were obtained.It was chosen to construct a herb-com-ponent-disease network and protein-protein interaction(PPI)network.Furthermore,DAVID database was used to perform gene ontology(GO)function and Kyo-to encyclopedia of genes and genomes(KEGG)path-way enrichment analyses.The molecular docking was presented by adopting Autodock Vina program to verify key targets.RNA-seq datawere downloaded from TC-GA database to obtain differential gene expression.Ka-planMeier(KM)analysis was performed to analyze the relationship between gene expression and overall sur-vival.Mouse subcutaneous tumor model of LLC was established.The effects of QRHXF on body weight,tumor volume and weight were monitored for pharmaco-dynamic analysis.Tumor tissues slides were stained with hematoxylin and eosin(HE)for histopathological examination.Immunohistochemistry(IHC)staining was employed for detecting Ki67 and EP300.Western blot was performed to measure the protein expression of TP53,CDK1 and NTRK1.Results The results of net-work pharmacology showed that a total of seven com-mon targets were screened from NSCLC and QRHXF,and the effect of QRHXF on anti-NSCLC may occur via multiple signaling pathways,including cell cycle.The results of molecular docking indicated that the main ac-tive components of QRHXF had low binding energy and stable docking conformation with the molecular target for treating NSCLC.According to bioinformatic analy-sis,there were significant differences in BRCA1,CDK1 and NTRK1 mRNA expression between tumor tissues and normal tissues,which were also prognostic factors for overall survival.Animal experimental research showed QRHXF inhibited subcutaneous tumor growth(P＜0.01)and improved the quality of life in mice with NSCLC.After QRHXF intervention,the density of tumor cells was significantly reduced,and necrotic are-as were increased.The expressions of Ki67 and EP300 were significantly decreased.Compared with the model group,Western blot showed up-regulation of TP53 and NTRKA(P＜0.05),whereas CDK1 were down-regu-lated(P＜0.05).Conclusion QRHXF exerted anti-NSCLC effects by regulating NTRK1,EP300,TP53,CDK1 and inducing cell cycle,cell cycle arrest and in-hibiting tumor growth,metastasis and angiogenesis.